Immunity Commons^™

Examining The Ligands, Location, And Function Of Toll-Like Receptor 10, Kiefer Keanu Tam

Master's Theses

Toll-like receptors are a class of innate immune pattern recognition receptors that detect pathogen-associated molecular patterns and regulate downstream inflammatory responses. Toll-like receptor 10 remains the only human TLR whose ligand specificity, cellular localization, and immunological function are not fully defined. Emerging evidence suggests that TLR10 may play an anti-inflammatory role and can heterodimerize with TLR2 to modulate immune signaling. Previous studies from our laboratory demonstrated that stimulation with heat-killed Mycobacterium tuberculosis promotes TLR2-TLR10 heterodimerization and trafficking to the cell surface. In this study, we expanded our ligand panel to include additional gram-positive bacteria, particularly anti-inflammatory probiotic species, to further …

Developing Antibodies Against Galectin-3 And Galectin-9 To Target Endometriosis, Ashleigh Burger, Noah Farnsworth, Jared J. Reisnouer, Cheyenne Vue

2026 Symposium

Endometriosis is a disease characterized by pelvic pain and the formation of endometrial-like tissue on the outside of the uterine lining. This condition affects nearly 10% of women across the globe and confirming whether someone has endometriosis requires visualization in surgery. While the specific causes of this disease remain unclear, the over-expression of the Galectins 3 and 9 in ectopic endometrial tissues suggests a role in the development and maintenance of the condition. Monoclonal antibodies (mAbs) are highly specific proteins with potential as diagnostic or treatment tools. The goal of this study is to generate antibodies against Gal3 and Gal9. …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Clinical Characteristics And Outcomes Of Pediatric Staphylococcal Scalded Skin Syndrome (Ssss) At An Inner-City Tertiary Care Center, Nina Kb Gust Md, Ashley Frei Bs, Rebecca M. Adams Bs, Elika Ridelman Phd, Christina Shanti Md, Ronald Thomas Phd, Jocelyn Y. Ang Md

Medical Student Research Symposium

Introduction

Staphylococcal Scalded Skin Syndrome (SSSS) is a blistering skin condition caused by a toxin-producing staphylococcus species. Epidemiologic studies on pediatric SSSS in the United States are limited, with a reported incidence of 7.67 cases per million children and 45.1 per million infants. Immature renal function, lack of protective antibodies, and increased exotoxin target desmoglein-1 are hypothesized to increase incidence in younger children. We aimed to determine clinical and microbiological characteristics of pediatric SSSS and factors that could help predict disease severity.

Methods

A retrospective chart review was performed for admitted patients under 18 years old diagnosed with SSSS from …

Mechanisms Of Macrophage Metabolic Activation And Paracrine Wnt Signaling In The Pathogenesis Of Systemic Sclerosis, Emily Ann Morris

Dartmouth College Ph.D Dissertations

Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology. We have previously shown that macrophages (MØs) play a critical role in its pathogenesis; however, the mechanisms driving MØ activation in SSc remain poorly understood. This dissertation investigates the molecular signaling pathways and biochemical mechanisms underlying profibrotic MØ activity in SSc.

First, I identify a novel MØ-specific effect of mycophenolate mofetil (MMF), the standard-of-care treatment for SSc. While MMF is a well characterized lymphostatic, my findings demonstrate that its active metabolite, mycophenolic acid (MPA), is also capable of directly inhibiting myeloid viability and profibrotic MØ activation by suppressing de …

Modulation Of Monocyte Effector Functions And Gene Expression By Human Cytomegalovirus Infection, Matthew Planchon, Jay Fishman, Joseph El Khoury

SKMC Student Presentations and Publications

Monocytes are crucial players in innate immunity. The human cytomegalovirus (CMV) infection has significant impacts on monocyte effector functions and gene expression. CMV, a β-herpesvirus, disrupts key monocyte roles, including phagocytosis, antigen presentation, cytokine production, and migration, impairing their ability to combat pathogens and activate adaptive immune responses. CMV modulates monocyte gene expression, decreasing their capacity for antigen presentation and phagocytosis while increasing pro-inflammatory cytokine production, which can contribute to tissue damage and chronic inflammation. CMV also alters monocyte migration to sites of infection while promoting trans-endothelial migration, thus aiding viral dissemination. Additionally, the virus affects reactive oxygen species (ROS) …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Mismatch Repair Deficient Neoantigen And Associated Circulating T-Cell Receptor Repertoires In Lynch Syndrome, Ana Bolivar

Dissertations and Theses (Open Access)

Lynch Syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome. It constitutes the perfect model to understand DNA mismatch repair deficient (MMRd) carcinogenesis, which underlies 15% of early-stage CRC. LS patients develop MMRd tumors with high loads of shared neoantigens (neoAgs), which are recognized by the immune system. Previous research has concentrated on discovering neoAgs and their potential as targets for vaccines in LS patients. However, these studies have primarily identified shared neoAgs from cancers, lacking detailed information on targetable neoAgs present in precancerous lesions. Understanding this landscape of pre-cancer derived neoAgs is crucial for intercepting cancer development …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Intergenerational Change In Hiv/Aids-Related Stigma In Cato Manor, Mijin Cho

Independent Study Project (ISP) Collection

In South Africa, the world’s epicenter of the HIV/AIDS pandemic, HIV-related stigma and stigma-enforcing stereotypes continue to serve as major health barriers to receiving adequate HIV prevention and treatment. While there continues to be a rise in research and advocacy, there is a need to study HIV stigma through a multigenerational lens that addresses the changing HIV/AIDS stigma in the post-apartheid era. Using qualitative methodology, this study aims to explore the generational differences in perceived HIV stigma between females in their 20s and above 50 years of age (as denoted by “50s+”) living in Cato Manor, South Africa. The study …

Phase 1a Clinical Study For Q-Griffithsin Intranasal Spray For Prevention Of Coronavirus, Megan Bezold, Kenneth Palmer, Nobuyuki Matoba, Elizabeth Cash

Posters-at-the-Capitol

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that causes acute respiratory disease with possible long-term complications, known as coronavirus disease 2019 (COVID-19). Griffithsin (GRFT; including the oxidation-resistant variant Q-GRFT used in this study) is an algal carbohydrate-binding protein exhibiting antiviral effects against many enveloped viruses, including all major variants of SARS- CoV-2 reported to date. Q-GRFT has been recombinantly manufactured in Nicotiana benthamiana plants, thoroughly purified, and formulated as an intranasal spray designed to be developed as a non-vaccine broad-spectrum prophylactic product for acute use. This is the first-in-human, randomized, double-blind, placebo-controlled study. The …

Elafibranor Modulates Ileal Macrophage Polarization To Restore Intestinal Integrity In Nash: Potential Crosstalk Between Ileal Il-10/Stat3 And Hepatic Tlr4/Nf-Κb Axes, Andrew Hakeem, Mohamed M. Kamal, Rasha A. Radwan, Basma A. Abdelrahman, Olfat A. Hammam, Mohey M. Elmazar, Aiman S. El-Khatib, Yasmeen M. Attia

Pharmacy

Experimental and clinical evidence implicate disrupted gut barrier integrity in provoking innate immune responses, specifically macrophages, towards the progression of non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptors (PPARs), a subset of the nuclear receptor superfamily, act to fine-tune several metabolic and inflammatory processes implicated in NASH. As such, the current study was carried out to decipher the potential role of dual PPAR α/δ activation using elafibranor (ELA) on ileal macrophage polarization (MP) and its likely impact on the liver in a NASH setting. To achieve this aim, an in vitro NASH model using fat-laden HepG2 cells was first used to validate …

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

Effectiveness And Safety Of Immunosuppressants And Biological Therapy For Chronic Spontaneous Urticaria: A Network Meta-Analysis, Wen-Kuang Lin, Shwu-Jiuan Lin, Woan-Ruoh Lee, Chia-Chieh Lin, Weei-Chin Lin, Hua-Ching Chang, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …

Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel

Department of Paediatrics and Child Health

Despite the uncertainty about the follow up of COVID-19 survivors, there is a growing body of evidence supporting specific interventions including pulmonary rehabilitation, which may lead to a reduced hospital stay and improved overall respiratory function. The aim of this short report was to assess the attitudes toward pulmonary rehabilitation following COVID-19 among Ecuadorian physicians. A cross-sectional study was conducted, in which a 5-question survey was used to assess the level of agreement to specific statements with a 5-point Likert scale. Out of the 282 participants, 48.2% (n=136) were male, with a mean of 12.6 (SD=11.3) years of experience. More …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Antibiotic resistance is one of the major global issues in the field of public health and medicine. Good antibiotic candidates need to be selectively toxic, inhibit cellular target, and effectively penetrate and accumulate in bacterial cells. The last factor is a formidable barrier in the development of antimicrobials effective in Gram-negative bacteria, due to the presence of two layers of cell envelope. The first half of my thesis focuses on understanding the permeation of small molecules through this formidable cell envelope, distribution inside the cell of Gram-negative bacteria, and design of novel methods to make small molecules effectively cross the …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Impact Of Physical Activity And Cardiorespiratory Fitness On Vascular Homeostasis In Premenopausal Women Consuming A Westernized High-Fat Meal, Lauren N. Pedersen

Theses and Dissertations

A large percentage of adults in industrialized nations consume a Westernized dietary pattern, which contributes to fasting dyslipidemia and increased risk for atherosclerotic cardiovascular disease. Evidence suggests that a single Westernized meal containing high saturated fat may induce alterations in blood lipids as well as disturb multiple factors regulating peripheral vascular homeostasis, including innate immune cell function, oxidative stress, and vascular function. Conversely, participation in acute and chronic exercise may beneficially impact an individual’s postprandial response. Therefore, this dissertation contains three manuscripts seeking to describe how acute exercise, cardiorespiratory fitness, and physical activity level impact the lipemic and vascular homeostatic …

Applying Immuno-Epidemiology Principles To Violence, Anna H. Sisk, Nina H. Fefferman, Judy Day, Patricia Bamwine

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties …

How Nutrition Can Help To Fight Against Covid-19 Pandemic, Faseeha Aman, Sadia Masood

Section of Internal Medicine

Currently Covid-19 pandemic is a leading challenge across the globe. It is mandatory to attain and maintain good nutritional status to fight against virus. Nutritional status of individual is affected by several factors such as age, sex, health status, life style and medications. Nutritional status of individuals has been used as resilience towards destabilization during this COVID-19 pandemic. Optimal nutrition and dietary nutrient intake impact the immune system, therefore the only sustainable way to survive in current context is to strengthen the immune system. There is no evidence found that supplement can cure the immune system except Vit C, which …